CA2896488A1 - Formation of semi-permeable porous artificial scab - Google Patents

Formation of semi-permeable porous artificial scab Download PDF

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Publication number
CA2896488A1
CA2896488A1 CA2896488A CA2896488A CA2896488A1 CA 2896488 A1 CA2896488 A1 CA 2896488A1 CA 2896488 A CA2896488 A CA 2896488A CA 2896488 A CA2896488 A CA 2896488A CA 2896488 A1 CA2896488 A1 CA 2896488A1
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Prior art keywords
scab
porous artificial
artificial scab
proteins
tissues
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CA2896488A
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French (fr)
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CA2896488C (en
Inventor
Parsival VEGA VILLAVICENCIO
Miguel Edgardo BATTISTA
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0085—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/7036—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0023—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • A61L2300/222—Steroids, e.g. corticosteroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/23—Carbohydrates
    • A61L2300/232—Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/43—Hormones, e.g. dexamethasone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/442—Colorants, dyes

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Materials For Medical Uses (AREA)
  • Prostheses (AREA)
  • Medicinal Preparation (AREA)

Abstract

A self-fixing semi-permeable porous artificial scab designed for protecting eroded or damaged surfaces. It can be applied to any living entity (including plants). The polymerized web of the scab forms upon application to the damaged surface by a reaction catalyzed by the action of the enzymes released by the lysed cells. Under this protective surface, the growth of new normal cells that can breathe freely without drying is promoted. It prevents loss of water, proteins and electrolytes, protects against infection and replaces the use of gauzes or dressings that damage new skin upon being removed. The red aqueous mixture applied by brushing or spraying, which has thixotropic properties, was obtained by the physicochemical interaction of the following compounds:
azosulfamide between 1 and 5 g%, gentian violet between 0.004 and 0.007 g%, dexamethasone between 0.001 and 0.003 g%, panthenol between 0.5 and 2 g% and gentamycin between 0.03 and 0.06 g%.

Description

FORMATION OF SEMI-PERMEABLE POROUS ARTIFICIAL SCAB
1. FIELD OF THE INVENTION
.=
The present invention relates to artificial cicatrization means by means of which a .5 substance is applied to the damaged surfaces, wounds, bums A-AB, after removing the necrotic = tissue and disinfecting the damaged or burnt zone.
2. PRIOR ART AND PROBLEMS TO BE SOLVED
The technique consists of the removal of the necrotic tissue from the injured zone and 0 subsequent application of the artificial covering mentioned in the title.
The preparation causes the formation of an artificial scab on the injured surface.
The problems to be solved are:
I. To replace the use of gauzes since they adhere to the damaged zone and cause lesions in the granulation zone when an attempt is made to remove them, thus causing defective ; 5 cicatrizations.
2. To avoid potential infections given that protection against external biological agents is provided.
3. To avoid the loss of body fluids and heat, resulting from the loss of the integrity of the mechanical barrier.
20 The porous artificial scab allows the formation of new tissue, allowing its natural respiration: during its regeneration and bringing about a faster development of cicatrization by avoiding disrupted processes such as the necrosis or the development of anaerobes, without the need to cover and without performing further treatments until the natural detachment of the "Scab."
4. AIM OF THE INVENTION
*To protect the lesion against infections and losses of fluids with an artificial scab, and thus the cicatrization is much more rapid and the new tissue is not defective.
*The usual cost of materials decreases, since once the scab is formed, further treatments are not necessary and the expulsion of this scab is natural.
0 5. DETAILED DESCRIPTION OF THE INVENTION
This aqueous thixotropic fluid which forms due to the reaction in the container is produced by the combination of 5 substances; azosulfamide between 1 and 5% +
gentian violet between 0.004 and 0.007% + dexamethasone, between 0.001 and 0.003% + panthenol between 0.5 and 2% + gentamycin, 0.03 and 0.06% having a red color., The preparation keeps its original properties for two years kept in caramel colored glass closed by screw cap or in pressure plastic at ambient temperature between 12 and 15 degrees centigrade.
In the case of extensive lesions, this red colored liquid is eliminated through the urine producing a reddish coloration without harmful effects, a fact that the users should be alerted to.
The necrotic tissues are removed, and a cleaning, degreasing and drying with petroleum ether is carried out.
The container is first shaken and it is applied on the injured surface with a clean metal spatula or by spray.

It can be applied to the eyes, ear and mucosas without the use of cleaning solvent and without risks.
Once applied to the surface of the living tissue, physicochemical reactions occur by enzymatic catalysis, generating a semicompact web by ionic and covalent bonds between its reactive groups.
This web adheres to the damaged tissues via exposed groups of said tissues.
The diagram below is intended to show the most probable structure.
d-Panthenol oxidizes enzymatically to form pantothenic acid.
This acid can react so as to form part of the coenzyme A or to bring about its bonding to l 0 the web mentioned in the scheme.
The sulfonyl groups, the carboxyl groups, the primary or secondary hydroxyl phenol or alcohol groups can react with exposed reactive groups of proteins or amino sugars allowing the attachment of the scab to the damaged skin which presents them at a high concentration.
The forces that confer strength to the structure are intramolecular or intermolecular and of ionic or covalent type.
The bonds of the web which presents numerous crossovers are stabilized between the various layers by hydrophobic interactions, by permanent or induced dipole-dipole hydrogen bonding, and other bonds.
This produces primary, secondary, tertiary and quaternary conformations that confer three dimensionality to the structure.
6. DESCRIPTION OF THE DRAWINGS
Drawing 1 Drawing 1 is intended to show a first-degree burn of the skin.
Drawing 2 This drawing is intended to show the description of the physicochemical reactions that produce a semicompact web by ionic and covalent bonds between its reactive groups; between the different components of the formula one can see peptide bonds, hydrophobic interactions, polar interactions, permanent or induced dipole-dipole bonds, hydrogen bonds, amide, ester, acid base bonds between the various components; this generates primary, secondary, tertiary and quaternary conformations which confers three dimensionality to the structure.
Drawing 3 Diagram of most likely chemical formula of semipermeable porous artificial scab.
Drawing 4 1 5 Gentian violet: Methyl violet, commonly also called crystal violet or gentian violet, is the name given to a group of chemical compounds used as pH indicators and dyes.
Gentian violet of (crystalline violet, methyl violet 10B, hexamethyl pararosaniline chloride) is an antifungal agent.
Drawing 5 Dexamethasone: Is a fluorinated corticoid having a long duration of action, a high anti-inflammatory and immunosuppressant power, and a low mineralocorticoid activity. It inhibits the synthesis of prostaglandins and leukotrienes, mediator substances in the vascular and cellular processes of inflammation and immunological response.

Drawing 6 Gentamycin: gentamycin is a broad-spectrum aminoglucoside antibiotic with bactericidal action. Mechanism of action: The aminoglucosides are transported actively through the bacterial
5 membrane, they bind irreversibly to one or more specific receptor proteins of the subunit 30S of the bacterial ribosomes and interfere with the initiation complex between mRNA
(messenger RNA) and the subunit 30S. The DNA can be read incorrectly, which gives rise to the production of nonfunctional proteins; the polyribosomes separate and are not capable of synthesizing proteins. This gives rise to an accelerated transport of aminoglucosides, as a result of which there is an increase in the rupture of the cytoplasmic membranes of the bacteria and consequent cell death.
Drawing 7 Panthenol: Panthenol, also referred to as D-pantothenyl alcohol or pantothenol, is a colorless, highly viscous and relatively sticky liquid. It is easily soluble in water and in alcohol (96 ). Panthenol dissolves without difficulty in the formulation of hair solutions, provided they are aqueous, hydroalcoholic or hydropropylene-alcoholic solutions.
Drawing 8 Azofulfamide: The sulfamides are basically derivatives of sulfanilamide which is a structural analog of PABA in which the carboxyl group is replaced by a sulfonyl group (SO2NH2). Thus, the sulfas act as competitive antagonists of PABA, preventing the synthesis of
6 dihydrofolate; in the absence of that metabolite, the synthesis of nucleic acids becomes impossible and as a result bacterial growth is inhibited (bacteriostatic effect).

Claims

7The scope of the invention and the way of producing it in injured tissues (Drawing I ) having been described and specified, the declaration is made to claim as exclusive right and property:
1. ¨ Self-fixing semipermeable porous artificial scab for protecting eroded or injured surfaces, which also allows the growth of new tissues under its protective covering. (SEE
DRAWING 2).
It is a composition characterized by the formation of a semipermeable porous artificial scab which is a web produced by the physical reactions between the mentioned compounds at the site of the application, catalyzed by the enzymes present at the injured site.
It would act like a cultured skin but is a chemical polymer in as much as a semipermeable porous artificial scab having these "chemical web" characteristics does not currently exist.
It also prevents the loss of water and electrolytes plasma and proteins.
The five substances described are characterized in that they are applied to a lesion (type A-AB burn or wound) react physicochemically by catalytic action of the damaged tissues thus generating a protective layer which prevents infections and the loss of plasma and proteins.
The new tissues do not lose their original structures due to the protection provided by this layer.
CA2896488A 2012-12-27 2013-11-04 Formation of semi-permeable porous artificial scab Expired - Fee Related CA2896488C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AR20120105043 2012-12-27
ARP120105043A AR089518A1 (en) 2012-12-27 2012-12-27 SEMIPERMEABLE PORTABLE ARTIFICIAL COSTRA
PCT/PE2013/000010 WO2014104898A2 (en) 2012-12-27 2013-11-04 Formation of semi-permeable porous artificial scab

Publications (2)

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CA2896488A1 true CA2896488A1 (en) 2014-07-03
CA2896488C CA2896488C (en) 2017-11-21

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CA2896488A Expired - Fee Related CA2896488C (en) 2012-12-27 2013-11-04 Formation of semi-permeable porous artificial scab

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US (2) US20160000963A1 (en)
EP (1) EP2939678B1 (en)
JP (1) JP6073500B2 (en)
CN (1) CN105073121B (en)
AR (1) AR089518A1 (en)
AU (1) AU2013368699B2 (en)
CA (1) CA2896488C (en)
ES (1) ES2633970T3 (en)
IL (1) IL239618B (en)
MX (1) MX2015007747A (en)
PE (1) PE20160748A1 (en)
RU (1) RU2015128753A (en)
UY (1) UY35111A (en)
WO (1) WO2014104898A2 (en)

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US3969498A (en) * 1973-09-13 1976-07-13 University Of The Pacific Dressing and method for treating a wound
JP3261807B2 (en) * 1992-06-09 2002-03-04 味の素株式会社 Gel composition having thixotropy
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CN103037858A (en) * 2010-07-02 2013-04-10 华柏恩视觉研究中心 Composition for prevention and treatment of contact lens papillary conjunctivitis and allergic eye disease
CN101947226A (en) * 2010-09-10 2011-01-19 李晓倩 Drops for treating pink eye

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WO2014104898A2 (en) 2014-07-03
AU2013368699A1 (en) 2015-07-16
US20190022274A1 (en) 2019-01-24
CA2896488C (en) 2017-11-21
PE20160748A1 (en) 2016-08-21
WO2014104898A3 (en) 2015-01-08
EP2939678B1 (en) 2017-04-19
AU2013368699B2 (en) 2017-08-10
ES2633970T3 (en) 2017-09-26
CN105073121A (en) 2015-11-18
MX2015007747A (en) 2015-09-04
AR089518A1 (en) 2014-08-27
US20160000963A1 (en) 2016-01-07
UY35111A (en) 2013-12-31
JP6073500B2 (en) 2017-02-01
EP2939678A4 (en) 2016-06-08
CN105073121B (en) 2018-12-04
EP2939678A2 (en) 2015-11-04
IL239618B (en) 2018-01-31
JP2016504357A (en) 2016-02-12
IL239618A0 (en) 2015-08-31
RU2015128753A (en) 2017-02-01

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